VCheng
ELITE MEMBER
- Joined
- Sep 29, 2010
- Messages
- 48,460
- Reaction score
- 57
- Country
- Location
http://www.economist.com/news/scien...e-understanding-evolution-may-deal-it-zoology
Antibiotic resistance
Zoology to the rescue
Evolution causes resistance. Understanding evolution may deal with it
From the print edition
MUCH is made, in academic circles, of the virtues of interdisciplinary research. Its practice is somewhat rarer. But fresh thinking and an outsider’s perspective often do work wonders, and that may just have happened in the field of antibiotic resistance.
Adin Ross-Gillespie of Zurich University is a zoologist, not a physician. But his study of co-operative animals such as meerkats and naked mole rats has led him to think about the behaviour of another highly collaborative group, bacteria. He and his colleagues have just presented, at a conference on evolutionary medicine in Zurich, a way of subverting this collaboration to create a new class of drug that seems immune to the processes which cause resistance to evolve.
Antibiotic resistance happens because, when a population of bacteria is attacked with those drugs, the few bugs that, by chance, have a genetic protection against their effects survive and multiply. As in most cases of natural selection, it is the survival of these, the fittest individuals, that spurs the process on. But Dr Ross-Gillespie realised that, in the case of bacteria, there are circumstances when the survival of the fittest cannot easily occur.
One of these is related to the way many bacteria scavenge a crucial nutrient, iron, from the environment. They do it by releasing molecules called siderophores that pick up iron ions and are then, themselves, picked up by bacterial cells. In a colony of bacteria, siderophore production and use is necessarily communal, since the molecule works outside the boundaries of individual cells. All colony members contribute and all benefit.
In theory, that should encourage free riders—bacteria which use siderophores made by others without contributing their own. In practice, perhaps because the bacteria in a colony are close kin, this does not seem to happen. But inverting free riding’s logic makes the system vulnerable to attack, for a bug that contributes more than its share does not prosper.
Following this line of thought Dr Ross-Gillespie turned to gallium, ions of which behave a lot like those of iron and can substitute for them in a siderophore, making it useless to a bacterium. In fact, siderophores bind more effectively with gallium than with iron, hijacking the whole process. A judicious dose of gallium nitrate can thus take out an entire bacterial colony, by depriving it of the iron it needs to thrive.
The crucial point is that, because siderophores are a resource in common, a mutated siderophore that did not bind preferentially to gallium would be swamped by the others, would fail to benefit the bug that produced it, and therefore would not be selected for and spread. At least, that was Dr Ross-Gillespie’s theory.
To test this theory out, he and his colleagues grew cultures of an infectious bacterium,Pseudomonas aeruginosa (pictured). They then exposed these cultures either to ciprofloxacin, an antibiotic, to gentamicin, another such, to both drugs at the same time, to saline as a control, or to gallium nitrate.
As they expected, both the antibiotics and the gallium nitrate curtailed the growth of Pseudomonas to start with. As they also expected, resistance to both of the antibiotics built up steadily over the 12-day course of the experiment. But nothing similar happened in the cultures exposed to gallium nitrate. These continued to be suppressed. And when the researchers took a closer look at what was going on, they found that not only were the bacteria in their gallium-laced samples starved of iron, but the bugs were also responding to the crisis by pouring their energy into producing more and more siderophores, thus hastening the colony’s demise.
What makes all this more than just a laboratory curiosity is that gallium nitrate is already an established drug. It has been used safely, and for a long time, to treat certain cancers and bone diseases. This suggests (though tests would need to be done) that it might be safe for use against infection. Dr Ross-Gillespie’s evolutionary analysis of how to attack antibiotic resistance might therefore have provided the breakthrough the field needs.
From the print edition: Science and technology
Antibiotic resistance
Zoology to the rescue
Evolution causes resistance. Understanding evolution may deal with it
From the print edition
MUCH is made, in academic circles, of the virtues of interdisciplinary research. Its practice is somewhat rarer. But fresh thinking and an outsider’s perspective often do work wonders, and that may just have happened in the field of antibiotic resistance.
Adin Ross-Gillespie of Zurich University is a zoologist, not a physician. But his study of co-operative animals such as meerkats and naked mole rats has led him to think about the behaviour of another highly collaborative group, bacteria. He and his colleagues have just presented, at a conference on evolutionary medicine in Zurich, a way of subverting this collaboration to create a new class of drug that seems immune to the processes which cause resistance to evolve.
Antibiotic resistance happens because, when a population of bacteria is attacked with those drugs, the few bugs that, by chance, have a genetic protection against their effects survive and multiply. As in most cases of natural selection, it is the survival of these, the fittest individuals, that spurs the process on. But Dr Ross-Gillespie realised that, in the case of bacteria, there are circumstances when the survival of the fittest cannot easily occur.
One of these is related to the way many bacteria scavenge a crucial nutrient, iron, from the environment. They do it by releasing molecules called siderophores that pick up iron ions and are then, themselves, picked up by bacterial cells. In a colony of bacteria, siderophore production and use is necessarily communal, since the molecule works outside the boundaries of individual cells. All colony members contribute and all benefit.
In theory, that should encourage free riders—bacteria which use siderophores made by others without contributing their own. In practice, perhaps because the bacteria in a colony are close kin, this does not seem to happen. But inverting free riding’s logic makes the system vulnerable to attack, for a bug that contributes more than its share does not prosper.
Following this line of thought Dr Ross-Gillespie turned to gallium, ions of which behave a lot like those of iron and can substitute for them in a siderophore, making it useless to a bacterium. In fact, siderophores bind more effectively with gallium than with iron, hijacking the whole process. A judicious dose of gallium nitrate can thus take out an entire bacterial colony, by depriving it of the iron it needs to thrive.
The crucial point is that, because siderophores are a resource in common, a mutated siderophore that did not bind preferentially to gallium would be swamped by the others, would fail to benefit the bug that produced it, and therefore would not be selected for and spread. At least, that was Dr Ross-Gillespie’s theory.
To test this theory out, he and his colleagues grew cultures of an infectious bacterium,Pseudomonas aeruginosa (pictured). They then exposed these cultures either to ciprofloxacin, an antibiotic, to gentamicin, another such, to both drugs at the same time, to saline as a control, or to gallium nitrate.
As they expected, both the antibiotics and the gallium nitrate curtailed the growth of Pseudomonas to start with. As they also expected, resistance to both of the antibiotics built up steadily over the 12-day course of the experiment. But nothing similar happened in the cultures exposed to gallium nitrate. These continued to be suppressed. And when the researchers took a closer look at what was going on, they found that not only were the bacteria in their gallium-laced samples starved of iron, but the bugs were also responding to the crisis by pouring their energy into producing more and more siderophores, thus hastening the colony’s demise.
What makes all this more than just a laboratory curiosity is that gallium nitrate is already an established drug. It has been used safely, and for a long time, to treat certain cancers and bone diseases. This suggests (though tests would need to be done) that it might be safe for use against infection. Dr Ross-Gillespie’s evolutionary analysis of how to attack antibiotic resistance might therefore have provided the breakthrough the field needs.
From the print edition: Science and technology
